AAV6-mediated delivery of a U7 exon skipping construct improves regional cardiac function in Golden Retriever muscular dystrophy dogs
نویسندگان
چکیده
S. C. Forbes, L. T. Bish, M. M. Sleeper, W. Mai, H. Sweeney, and G. A. Walter Department of Physical Therapy, University of Florida, Gainesville, FL, United States, Department of Physiology, University of Pennsylvania, Philadelphia, PA, Department of clinical studies, University of Pennsylvania, Philadelphia, PA, School of Veterinary Medicine, University of Florida, Philadelphia, PA, Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL
منابع مشابه
Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping.
Most mutations in the dystrophin gene create a frameshift or a stop in the mRNA and are associated with severe Duchenne muscular dystrophy. Exon skipping that naturally occurs at low frequency sometimes eliminates the mutation and leads to the production of a rescued protein. We have achieved persistent exon skipping that removes the mutated exon on the dystrophin messenger mRNA of the mdx mous...
متن کاملA Duchenne Muscular Dystrophy Gene Hot Spot Mutation in Dystrophin-Deficient Cavalier King Charles Spaniels Is Amenable to Exon 51 Skipping
BACKGROUND Duchenne muscular dystrophy (DMD), which afflicts 1 in 3500 boys, is one of the most common genetic disorders of children. This fatal degenerative condition is caused by an absence or deficiency of dystrophin in striated muscle. Most affected patients have inherited or spontaneous deletions in the dystrophin gene that disrupt the reading frame resulting in unstable truncated products...
متن کاملSerum profiling identifies novel muscle miRNA and cardiomyopathy-related miRNA biomarkers in Golden Retriever muscular dystrophy dogs and Duchenne muscular dystrophy patients.
Duchenne muscular dystrophy (DMD) is a fatal, X-linked neuromuscular disease that affects 1 boy in 3500 to 5000 boys. The golden retriever muscular dystrophy dog is the best clinically relevant DMD animal model. Here, we used a high-thoughput miRNA sequencing screening for identification of candidate serum miRNA biomarkers in golden retriever muscular dystrophy dogs. We confirmed the dysregulat...
متن کاملThe cranial sartorius muscle undergoes true hypertrophy in dogs with golden retriever muscular dystrophy.
The degree of atrophy or hypertrophy of selected pelvic limb muscles was determined in the canine homologue of Duchenne muscular dystrophy. While most muscles were atrophied, the caudal and cranial sartorius were hypertrophied. Cranial sartorius weights were corrected for body weight and endomysial space to determine true muscle weights (g/kg; mean+/-SD) in three golden retriever muscular dystr...
متن کاملRescue of severely affected dystrophin/utrophin-deficient mice through scAAV-U7snRNA-mediated exon skipping
Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by mutations in the dystrophin gene that result in the absence of functional protein. Antisense-mediated exon skipping is one of the most promising approaches for the treatment of DMD and recent clinical trials have demonstrated encouraging results. However, antisense oligonucleotide-mediated exon skipping for DMD still...
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